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Molecular and functional analysis of presomitic mesoderm patterning and segmentation during murine embryogenesis


Research objectives and content
Somites constitute the most obvious segmental pattern in vertebrate embryos. Each segment represents a clonal compartm and altogether they form the axial skeleton, the dermis of the back and all striated muscles of adult animals. Somites are therefore essential for establishment and proper development of the basic body plan. During embryogenesis, bi-lateral pairs of somite appear in a rostro-caudal order by progressive segmentation of the anterior presomitic paraxial mesoderm. However, little is known about the genes and molecular mechanisms controlling segmentation in vertebratesDr. Herrmann is conducting a large scale expression screen using whole-mount in situ hybridisation on mouse embryos to identify genes specifically expressed during somitogenesis. I screened 800 cDNAs and found novel genes specifically expressed in the developing somites. In particular, the expression patterns of 2 novel genes strongly suggests their involvment in the presomitic mesoderm segmentation process.I will determine the role played by these two genes during somitogenesis by creating loss-of-function alleles by homologous recombination into mouse ES cells. The characterization of these two genes will also include a more complete molecular analysis, the generation of antibodies and extended expression analysis during development of normal and Brachyury and deltalike 1 mutant embryos. In parallele, I will also continue the expression screen on 1000 additional cDNAs clones.
Training content (objective, benefit and expected impact)
The originality of this approach is in the possibility to screen large number of cDNAs and in the fact that the newly identified genes are readily available to be used as molecular markers or to initiate functional studies. I will gain valuable experience in functional analysis strategies that I can use later in my carreer for the study of other developmental or ontogenic processes. This formation will be a good complement to my previous training with Dr. J. Rossant using gene trap vectors. The screen provides novel molecular markers and potential regulators and targets of important developmental genetic pathways. Expression of known genes as well as novel genes is of importance for the future development of functional genomics. It will also benefit the scientific community as the results coming out of this screen will be made available on-line the form of a public database.
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Max-Planck-Gesellschaft zur Forderungder Wissenschaften e.V.
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